Therapy-related myeloid neoplasm is the term recently proposed by the World Health Organization to cover the spectrum of malignant disorders previously described as therapy-related myelodysplastic syndrome or therapy-related acute myeloid leukemia. In this perspective article, Dr. Larson explores the important question of whether the poor prognosis of these conditions reflects t-MN per se or, rather, associated findings such as complex cytogenetics that are also seen, although less frequently, in de novo myeloid neoplasms. See related article on page 542.